On the 400, which was released last fall, I could only find three men who became rich by spearheading the development and marketing of a new drug:

The richest is Patrick Soon-Shiong, worth $5.2 billion, who made much of his wealth from a hospital generics business but also invented a drug called Abraxane; he sold the company that made it to biotech giant Celgene last year for $2.9 billion last year.

Randal J. Kirk, worth $2.2 billion, made his fortune by running and then selling off two makers of psychiatric drugs, New River Pharmaceuticals (attention deficit disorder) and Clinical Data (Vyvanse, for depression.)

Michael Jaharis, worth $1.9 billion, launched a company called Kos Pharmaceuticals in 1988 that developed a prescription version of the B vitamin niacin, to raise good cholesterol. It was sold to Abbott Laboratories in 2006 for $4.6 billion.

If we go into the deeper pool of the billionaires list, which includes 1210 people with fortunes of over $1 billion, there still aren't many candidates. There's Ernesto Berteralli, who inherited Swiss drug maker Serono and helped build it into Germany's biggest biotech. He's the richest health care-related billionaire, with a $10 billion fortune.Curt Englehorn accomplished a similar feat with Boeringher Manheim, sold to Roche in 1997. But I can't find any other candidates. Again, it looks like inventing drugs is fantastically unlikely to make you rich.

Part of the reason is that health care in general is a pretty bad choice of a sector if you want to make a mega-fortune. Only 14 of the 400, or 3.5%, get their money from health care or medicine. On the 1210-person billionaires list, about 60, or 5%, made their money in health care. That compares to 90 billionaires from the tech industry, 80 from finance, and 140 who make their money from investments. (All that data is available by using our lists -- and counting.)

Bertarelli, the top dog among health care billionaires, rates only 81st on the full list list. There are four technology billionaires and nine who made their money through investments who are richer than anybody who made their fortune in the health care field.

Yet even in the general area of health care, drug development doesn't do well. Many people have made billion-dollar fortunes through the pharmaceutical business. But they have done it largely with generic drugs, or with drug whole sale. There are also several, like Alfred Mann and Gary Michelson, who made their fortunes in medical devices.

I emailed Randal Kirk to ask him why there were so few medicine-making billies. Was it that Forbes was missing people? (There have been enough private deals in biotech with undisclosed sums that this seems possible, but the beneficiaries would be at the low end of our lists.) Do researchers in biotech lack financial acumen?

Kirk dismissed those possibilities out of hand, and told me to ask the question differently. What do he, Jaharis, and Soon-Shiong have in common?

Kirk writes:

I think it is this: Each has largely devoted himself (and his capital) to one or only a very few highly concentrated positions in companies that they developed over years of effort. In my own case, I bought my first share of Clinical Data in 1999 and kept investing in the company through 2009. Similarly, New River Pharmaceuticals was founded by me in 1996 (IPO’d in 2004 and sold to Shire in 2007). In New River’s IPO not only did I not sell shares but was the second largest purchaser of shares that were then sold.

So why may that be a winning strategy? Aside from the more obvious advantages that naturally may flow from an intensely interested, dedicated and (I would like to think) capable shareholder, the length of the holding periods to which I refer may actually have been required in biotech because the product development cycle times have been so long.

This in itself shows why biotech hasn't produced a Bill Gates, a Sergey Brin, or a Mark Zuckerberg. All of those men were able to make their fortunes by deploying their technical expertise quickly, with low barriers to entry. They might have needed outside investors, but they did not have to give up their controlling stakes. They made the right bet, and they got rich.

In biotech, by contrast, investors have to make the right bet and stick with it for years. Making matters worse, not only are the time frames of drug development measured in years or decades, the cost can be extremely high. A cheap drug development program can cost $50 million; an expensive one, for a heart drug, for instance, might cost well more than $1 billion. Most inventors who manage to invent a new drug and hold on to some interest in it cash out before the medicine gets to market or end up so diluted that they don't make that much money. An odd result of this is that the men who have become billionaires by developing medicines have done so based on drugs that wouldn't make anybody's short list of the most important or best-selling medicines.